DESCRIPTION (provided by investigator): Each year more than 2 million couples in the US who want to have children are infertile, and over 2 million conceptions are lost before the twentieth week of gestation. About 40 percent of cases of human infertility are due to male factors. Errors in chromosome segregation during meiosis result in structural aberrations and imbalances in chromosome number known as aneuploidy. Most new gene mutations seen in offspring and most abnormalities in the numbers of the sex chromosomes arise from the father's sperm. There is emerging evidence that environmental chemicals can adversely affect spermatogenesis and the occurrence of chromosomal aberrations, possibly through mechanisms of endocrine hormone modulation. The proposed study is efficient and economic in that it will leverage existing medical interview data and archived biological specimens to investigate novel relationships between sperm aneuploidy and common environmental exposures, specifically polychlorinated biphenyls (PCBs), DDT, organophosphates (OPs), and pyrethroids (PYRs). Archived semen, serum, and urine samples are available from 500 men who have attended a large hospital based fertility clinic for fertility evaluation. Exposures to PCBs, DDT, OPs and PYRs have been well characterized in this population, and prior work from our group has found associations between organochlorines and inferior semen quality and contemporary use pesticides and DNA damage. The question remains as to whether these exposures impact sperm aneuploidy. We have validated an automated system that makes quantifying sperm aneuploidy in large sample sizes feasible so that the full complement of archived samples can be studied and novel relationships between sperm aneuploidy and common environmental exposures can be quantified. This study will also more fully characterize aneuploidy as an effect biomarker by exploring its comparability with DNA damage and common indicators of semen quality. PUBLIC HEALTH RELEVANCE: Environmental chemicals that are common in today's environment may be having an impact on male reproductive health. This study investigates whether chemicals common in our daily environment can affect male fertility and potential risks for birth defects.